Eph是酪氨酸受体家族中的一大类，是潜在的药物治疗靶标，但其家族成员在肿瘤中发挥的具体作用及分子机制却知之甚少。申请人前期发现该家族成员EphA3、EphB6突变或异常表达可影响大肠上皮细胞生物学行为，在细胞恶性增殖、侵袭和转移中发挥重要作用，提示EphA3和EphB6可能参与了大肠细胞恶性转化和演进过程。本项目拟在已有工作基础上，采用定点突变技术构建EphA3和EphB6常见突变体，以4种分别代表大肠癌不同病理进程的含有APC或/和RAS突变的转基因鼠模式细胞为材料，采用基因芯片与蛋白质组学，结合生物信息学技术，研究EphA3和EphB6突变或异常表达对大肠上皮细胞恶性转化及演进的影响，探讨其在大肠癌发生发展过程中的作用机制，阐明其影响的信号转导通路，为大肠癌的预防、诊断和治疗提供理论基础和新思路。

As one of the largest class of tyrosine receptor family, Eph is a potential drug target for treatment, but the specific role and its molecular mechanisms of its family members in tumor are poorly understood.Our preliminary study found that abnormal expression of EphA3 or EphB6 can influence the biology behaviors of colorectal epithelial cell, including cell proliferation, invasion and metastasis. It suggestes that EphA3 and EphB6 may be involved in malignant transformation and evolution of colorectal cells. On the basis of early work, by using site-directed mutagenesis technology, the applicants will construct a series of relatively common mutant recombinants of EphA3 and EphB6. Four colorectal epithelial cell models from transgenic rat on behalf of colorectal cancer in different pathological processes and different context of APC and Ras gene expression,are used as the experimental object. The role of EphA3 and EphB6 on malignant transformation and evolution of colorectal epithelial cell will be studied by using microarray,proteomics and bioinformatics. Further study will be carried out to clarify its signal transduction pathways and molecular mechanism. The above study will provide the theoretical basis and new ideas for the prevention, diagnosis and treatment for colorectal cancer.